IgA nephropathy caused by unusual polymerization of IgA1 with aberrant N-glycosylation in a patient with monoclonal immunoglobulin deposition disease.
IgA nephropathy caused by unusual polymerization of IgA1 with aberrant N-glycosylation in a patient with monoclonal immunoglobulin deposition disease.
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DOI：
10.1371/journal.pone.0091079
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Narimatsu H
中科院分区：
文献类型：
--
作者：
Narimatsu Y;Kuno A;Ito H;Kaji H;Kaneko S;Usui J;Yamagata K;Narimatsu H
免疫球蛋白A肾病（IgAN）是一种慢性肾小球肾炎，其特征在于伊加免疫复合物在肾小球区域的沉积。IgAN的原因尚不清楚，但已提出多种机制。我们先前报告了一个罕见的情况下，系膜增生性肾小球肾炎的患者与单克隆免疫球蛋白沉积疾病与单克隆IgA 1。在这项研究中，我们进行了详细的分析，血清IgA 1从这个病人相比，从mIgA浆细胞疾病患者没有肾脏受累和健康志愿者。我们发现不寻常的聚合与额外的N-糖基化独特的IgA 1在这个病人，这是从已知的病因不同。通过凝集素微阵列的IgA 1的聚糖分析揭示了花紫藤凝集素（WFA）的强烈信号。通过破坏IgA 1的天然构象降低了该信号，表明不同的聚糖谱反映了IgA 1的构象变化，包括在重链和轻链上检测到的作为额外N-聚糖的聚糖构象。这种不寻常的聚合状态的IgA 1会导致凝集素的结合亲和力的增加。WFA特异性识别高度聚合和糖基化的IgA 1。我们的分析结果在罕见的情况下，单克隆免疫球蛋白沉积疾病的患者表明，形成异常聚合的IgA 1是由不同的机制，包括多个结构改变的聚糖，这有助于IgA 1沉积和系膜增殖。
Immunoglobulin A nephropathy (IgAN) is a form of chronic glomerulonephritis characterized by the deposition of IgA immune complexes in the glomerular region. The cause of IgAN is unknown, but multiple mechanisms have been suggested. We previously reported a rare case of mesangioproliferative glomerulonephritis in a patient with monoclonal immunoglobulin deposition disease associated with monoclonal IgA1. In this study, we performed the detailed analyses of serum IgA1 from this patient in comparison with those from patients with mIgA plasma cell disorder without renal involvement and healthy volunteers. We found unusual polymerization of IgA1 with additional N-glycosylation distinctive in this patient, which was different from known etiologies. Glycan profiling of IgA1 by the lectin microarray revealed an intense signal for Wisteria floribunda agglutinin (WFA). This signal was reduced by disrupting the native conformation of IgA1, suggesting that the distinct glycan profile was reflecting the conformational alteration of IgA1, including the glycan conformation detected as additional N-glycans on both the heavy and light chains. This unusually polymerized state of IgA1 would cause an increase of the binding avidity for lectins. WFA specifically recognized highly polymerized and glycosylated IgA1. Our results of analysis in the rare case of a patient with monoclonal immunoglobulin deposition disease suggest that the formation of unusually polymerized IgA1 is caused by divergent mechanisms including multiple structural alterations of glycans, which contributes to IgA1 deposition and mesangium proliferation.
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DOI：
10.1083/jcb.200808124
发表时间：
2009-03-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Glozman R;Okiyoneda T;Mulvihill CM;Rini JM;Barriere H;Lukacs GL
通讯作者：
Lukacs GL
影响因子：
2.9
作者：
GERKEN, TA;BUTENHOF, KJ;SHOGREN, R
通讯作者：
SHOGREN, R
影响因子：
2.1
作者：
Hashimoto, Ryo;Toda, Tosifusa;Mori, Mayumi
通讯作者：
Mori, Mayumi
影响因子：
7
作者：
Kuno, Atsushi;Kato, Yukinari;Hirabayashi, Jun
通讯作者：
Hirabayashi, Jun
影响因子：
48
作者：
Kuno, A;Uchiyama, N;Hirabayashi, J
通讯作者：
Hirabayashi, J